Second-Line Zanubrutinib Improves OS in R/R Mantle Cell Lymphoma

"...Zanubrutinib is an effective and well-tolerated therapeutic option for [relapsed/refractory] MCL and an early treatment with zanubrutinib tends to have better survival outcomes," according to the study authors.

Treatment with zanubrutinib (Brukinsa) produced significant improvements in overall survival (OS) among patients with relapsed/refractory mantle cell lymphoma (MCL) when administered in the second-line setting compared with later lines of therapy, according to an analysis of pooled data from the phase 1 BGB-3111-AU-003 study (NCT02343120) and the phase 2 BGB-3111-206 study (NCT03206970).

The median OS in the overall population was not estimable (NE) after a median follow-up of 35.2 months. Investigators highlighted a significant OS improvement with zanubrutinib in the second-line setting vs later lines (HR, 0.459; 95% CI, 0.215-0.980; P = .044). The OS rate at 36 months in the overall population was 66.8% (95% CI, 58.3%-76.5%). Additionally, the 36-month OS rates after weighting in the second-line and later-line treatment groups, respectively, were 82.0% (95% CI, 71.7%-94.1%) compared with 66.5% (95% CI, 56.0%-79.5%).

Investigators reported a median progression-free survival (PFS) of 26.5 months (95% CI, 16.8-NE) in the overall pooled population prior to weighting. Additionally, PFS was similar between the second-line and later-line groups after weighting (HR, 0.78; 95% CI, 0.443-1.373; P = .389). The median PFS in the second-line and later-line groups, respectively, was 27.8 months vs 22.1 months post-weighting. The 36-month PFS rates in each respective group after weighting were 44.8% (95% CI, 31.8%-66.9%) vs 35.4% (95% CI, 25.0%-52.3%).

The objective response rate (ORR) was 84.8% (95% CI, 76.8%-90.9%) in the overall population. Additionally, investigators reported ORRs of 88.6% in the second-line group and 85.7% in the later-line group after weighting. Treatment with zanubrutinib yielded a median duration of response (DOR) of 30.6 months (95% CI, 23.1-NE) in the overall population. In the second-line and later-line groups, respectively, the median DORs were 25.2 months vs 25.1 months after weighting.

“Subsequent prospective studies with larger sample size will further help define the optimal position of zanubrutinib in the treatment sequence of [relapsed/refractory] MCL,” the study authors wrote. “Concluding, zanubrutinib is an effective and well-tolerated therapeutic option for [relapsed/refractory] MCL and an early treatment with zanubrutinib tends to have better survival outcomes.”

Investigators of this study assessed outcomes of patients with relapsed/refractory MCL who received zanubrutinib in the BGB-3111-AU-003 and BGB-3111-206 studies. Patients were divided into 2 groups based on whether they received treatment in the second-line or later-line settings.

The study’s primary end point was OS. Secondary end points included PFS, ORR based on Lugano classification, DOR, and safety.

Patients with no missing baseline covariates including ECOG performance status, disease stage, blastoid variant, and MCL International Prognostic Index (MIPI) were eligible for inclusion in this study.

The study population consisted of 112 patients, including 41 in the second-line group and 71 in the later-line group. In the second-line and later-line groups, respectively, 46.3% and 31.0% of patients were 65 years and older; 26.8% and 18.3% had high-risk MIPI scores; 51.2% and 64.8% had extranodal disease; and 31.7% and 40.8% had bulky disease. After using an inverse propensity score weighting method to balance baseline covariates between the groups, investigators reported that 30 patients received second-line zanubrutinib and 61 received treatment in later-line settings.

Investigators observed at least 1 any-grade adverse effect (AE) in 96.4% of patients; 53.6% experienced at least 1 grade 3 or higher toxicity. Any-grade AEs occurred in 94.6% of patients in the second-line group and 98.2% of the later-line group after weighting. Additionally, 56.9% and 47.8% of patients in each respective treatment group had at least 1 grade 3 or higher AE. The safety profile was generally comparable between the second-line and later-line groups before and after weighting.

Reference

Song Y, Zhou K, Zou D, et al. Long-term outcomes of second-line versus later-line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: an updated pooled analysis. Cancer Med. Published online September 14, 2023. doi:10.1002/cam4.6473